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Prospective, randomized comparison of high-frequency oscillation and conventional ventilation in candidates for extracorporeal membrane oxygenation.

OBJECTIVE: To compare the safety and efficacy of high-frequency oscillation (HFO) with conventional ventilation in the treatment of neonates with respiratory failure. DESIGN: We conducted a multicenter, prospective, randomized trial. Patients were stratified according to pulmonary diagnosis and then were randomly selected for conventional ventilation or HFO. A balanced crossover design offered patients who met criteria of treatment failure a trial of the alternative mode of ventilation. SETTING: Four tertiary, level 3 neonatal intensive care units accepting regional referrals for extracorporeal membrane oxygenation. PATIENTS: Neonates were eligible for enrollment if their gestational age was > 34 weeks, their birth weight was > or = 2 kg, they were < 14 days of age, they required fractional inspired oxygen > 0.50 and a mean airway pressure > 0.98 kPa (10 cm H2O) to support adequate oxygenation, and they required a peak inspiratory pressure > 2.9 kPa (30 cm H2O) and a rate > 40 breaths per minute to support adequate ventilation. Exclusion criteria were lethal congenital anomalies, profound shock, need for cardiopulmonary resuscitation, and failure to obtain consent. MAIN RESULTS: Of 79 patients studied, 40 were assigned to conventional ventilation and 39 to HFO. Neonates randomly assigned to HFO required higher peak pressure (3.8 +/- 0.5 vs 3.3 +/- 0.8 kPa, 39 +/- 5 vs 34 +/- 8 cm H2O; p = 0.004) and more often met extracorporeal membrane oxygenation criteria (67% vs 40%; p = 0.03) at study entry than did those given conventional ventilation. Twenty-four patients (60%) assigned to conventional ventilation met treatment failure criteria compared with 17 (44%) of those assigned to HFO (not significant). Of the 24 patients in whom conventional ventilation failed, 15 (63%) responded to HFO; 4 (23%) of the 17 in whom HFO failed responded to conventional ventilation (p = 0.03). There were no differences between the two groups with respect to outcome, need for extracorporeal membrane oxygenation, or complications. CONCLUSIONS: We conclude that HFO is a safe and effective rescue technique in the treatment of neonates with respiratory failure in whom conventional ventilation fails.

Extracorporeal Membrane Oxygenation↗

Effects of simulated mouth-to-mouth ventilation during external cardiac compression or active compression-decompression in a swine model of witnessed cardiac arrest.

STUDY OBJECTIVE: To assess the effects of simulated mouth-to-mouth (MTM) ventilation on blood gases, gas exchange, and minute ventilation during external cardiac compression (ECC) or active compression-decompression (ACD) in a swine model of witnessed cardiac arrest and bystander CPR. METHODS: Twenty swine were anesthetized, intubated, ventilated with room air, and monitored for aortic and right atrial pressure and blood gas sampling. After 1 minute of ventricular fibrillation cardiac arrest, ECC or ACD was manually performed at a rate of 100 per minute for 12 minutes. Animals in the room air group had their endotracheal tubes open to air, whereas those in the MTM group were mechanically ventilated with a gas mixture of 16% oxygen and 4% carbon dioxide. Arterial and venous PO2, PCO2, and pH values; oxygen consumption (VO2); carbon dioxide production (VCO2); and minute ventilation (VE) were measured at baseline and 1, 5, 9, and 13 minutes after induction of cardiac arrest. RESULTS: MTM ventilation did not alter arterial or venous PO2 values in comparison with room air but did result in higher arterial PCO2 values at 5 and 9 minutes (although the mean PCO2 was 40 mm Hg or less [5.3 kPa] in all groups) and significant central venous hypercarbic acidosis at 9 and 13 minutes. Arterial PO2 values were greater in the ACD than the ECC groups at 5, 9, and 13 minutes, although all groups maintained acceptable PO2 (mean values > or = 60 mm Hg [8.0 kPa]) through 9 minutes of CPR and through 13 minutes in all but the ECC-room air group. PCO2 values were lower in the ACD groups beyond 1 minute, with the ACD-room air group showing extreme hyperventilation (mean PCO2 < or = 20 mm Hg [2.7 kPa]). MTM ventilation resulted in negative VO2 and VCO2 for the first few minutes, reflecting changes in pulmonary gas stores. As equilibrium was approached, VO2 and VCO2 approached zero in all groups, reflecting low cardiac output. MTM ventilation did not improve VE over room air at any time during ACD. It did improve VE during ECC, but only at the 12th interval. CONCLUSION: In this swine model of witnessed CPR, simulated MTM ventilation was not beneficial for blood gases, gas exchange, or ventilation during ECC or ACD CPR.

Animals↗

Helium-oxygen ventilation.

Because of its low density, the He/O2 mixture markedly affects the dynamics of gas-flow, increasing inspiratory and expiratory flows, reducing WOB and respiratory acidosis, and relieving dyspnea in various clinical situations associated with obstructive airway disease. The magnitude of these changes varies according to the proportion of turbulent, transitional, and laminar flow conditions. These effects, however, last only as long as the patient breathes the He/O2 mixture, because it has no curative effect on the cause of airway obstruction. Thus, He/O2 ventilation is mostly useful while awaiting the effects of more definitive treatment. Evidence shows that He/O2 ventilation can improve pathophysiologic and clinical parameters in spontaneously breathing patients with upper airway obstruction, asthma. COPD, bronchopulmonary dysplasia. and bronchiolitis. Furthermore. He/O2 ventilation may prove to be a valuable adjunct in decompensated COPD patients, during both NIV and conventional mechanical ventilation. Despite promising results, however, there are two primary pitfalls to He/O2 ventilation. First, the consequences of the physical properties of the He/O2 mixture on various ventilator functions, the major differences between machines, and the correction factors to apply (if necessary) should be known. Second, in this age of cost control, particular attention should be paid to the cost-benefit ratio of He/O2 ventilation. Indeed, despite clinical evidence that the pathophysiologic principles on which He/O2 ventilation rests can be translated into favorable short-term physiologic and subjective effects, there is presently no evidence of a significant effect on patient outcome. Hence, before He/O2 ventilation can be recommended for widespread use, prospective outcome studies should be conducted in patients who suffer from the conditions discussed in this article to identify which, if any, are most likely to receive a benefit. Meanwhile, the authors recommend that He/O2 ventilation be reserved for patients who have a severe condition and who do not respond to the classic validated treatment modalities.

Clinical Trials as Topic↗

Bacterial contamination in a modern operating suite. 1. Effect of ventilation on airborne bacteria and transfer of airborne particles.

The effect of ventilation on airborne contamination was studied in a new operating suite containing operating rooms with conventional ventilation (17-20 turnovers/h) and operating rooms with zonal ventilation, where the turnover in the central part of the room was approximately 80/h. The efficacy of the ventilation was first examined with gas tracer experiments and found satisfactory. Experiments using potassium iodide particles showed the transfer between adjacent rooms in the suite to be less than 10(-3)% with closed doors and from 1% to 2.5 x 10(-2)% when the doors were opened once a minute. The transfer between two adjacent operating rooms was calculated to be approximately 10(-4)%. There is thus little risk of spread of airborne infection between operating rooms.Experiments with potassium iodide particles showed that in operating rooms with zonal ventilation the particle concentration in the centre of the room was about one-tenth that in the periphery; in conventionally ventilated operating rooms the concentration was about one-half. With bacteria-carrying particles generated by human activity the concentration in the centre of operating rooms with zonal ventilation was about half that in the periphery both during experimental activity and operations; in conventionally ventilated operating rooms it was about equal in both cases. Bacterial counts at the periphery were found to be lower in rooms with zonal ventilation ( approximately 50 c.f.u./m(3)) than in conventionally ventilated ( approximately 70 c.f.u./m(3)).

Air Microbiology↗

Enhancement of mechanical ventilation of neonates by computer technology.

Mechanical ventilation is often required in the extremely small preterm infant because of transient failure of the immature control of breathing system, chest wall instability, weakness of the respiratory pump, and chronic lung disease. To better address some of these issues, computer algorithms have been developed for continuous automated control of the arterial hemoglobin oxygen saturation (by changing the fraction of inspired oxygen), of the tidal volume (by varying peak inspiratory pressure), and of minute ventilation (by changing respirator rate). Feasibility studies have shown that closed-loop computer control of physiologic target variables may stabilize oxygenation, decrease the transpulmonary pressure cost of ventilation, and expedite weaning from mechanical ventilation. In addition to synchronizing the upstroke in ventilator pressure with the onset of the spontaneous respiratory effort, computer technology may render the changeover from inspiration to expiration patient-cycled in a mode called pressure support ventilation. Proportional assist ventilation enhances ventilation in near perfect synchrony with the patient's spontaneous respiratory efforts. With this mode, the clinician selects gains for elastic and/or resistive unloading to tailor the ventilator pressure contour to the specific derangement in pulmonary mechanics (restrictive and/or obstructive). Most of these newer ventilatory strategies are as yet unproven and require randomized, controlled clinical study. Similarly, although on-line pulmonary mechanics monitoring during mechanical ventilation has become available with the adent of computer technology, its clinical utility is still not well established.

Algorithms↗

Nurse-led weaning from mechanical ventilation: where's the evidence?

BACKGROUND: Several authors have suggested clinical protocols as a means of shortening ventilation time and the important role of the nurse in reducing ventilation time has also been highlighted. Despite the many references in the literature to reducing weaning times using clinical protocols, it is not clear whether nurse-led weaning strategies hasten weaning from mechanical ventilation compared with physician-led care. OBJECTIVE: to systematically review the published literature to answer the question: Does nurse-led weaning from mechanical ventilation reduce duration of ventilation compared with doctor-led care? DATA SOURCES: MEDLINE, CINHAL, EMBASE, Cochrane Library, Best Evidence, hand search, expert opinion, controlled trials register. STUDY SELECTION: randomized controlled trials (RCTs) and cohort studies where nurses or respiratory therapists lead the weaning from mechanical ventilation; duration of ventilation must be stated. DATA EXTRACTION: performed by the author, who extracted data on statistical significance of the difference in duration of ventilation between control and trial groups, complication rates (such as reintubation) and mortality. DATA SYNTHESIS: statistical synthesis was not attempted but narrative synthesis was performed. RESULTS: only 1 randomized controlled trial and 2 cohort studies were found where nurses or respiratory therapists led weaning using a protocol. Two studies showed reduction in ventilation time without additional complications; the third study had the weakest evidence, because it was retrospective, and showed no difference between control and treatment groups. CONCLUSIONS: There is limited evidence suggesting that nurse-led weaning may reduce ventilation time; however, it is not clear whether it was the nurse-led aspect or the clinical protocol that produced the effect.

Clinical Protocols↗

Withdrawal of mechanical ventilation in anticipation of death in the intensive care unit.

BACKGROUND: In critically ill patients who are receiving mechanical ventilation, the factors associated with physicians' decisions to withdraw ventilation in anticipation of death are unclear. The objective of this study was to examine the clinical determinants that were associated with the withdrawal of mechanical ventilation. METHODS: We studied adults who were receiving mechanical ventilation in 15 intensive care units, recording base-line physiological characteristics, daily Multiple Organ Dysfunction Scores, the patient's decision-making ability, the type of life support administered, the use of do-not-resuscitate orders, the physician's prediction of the patient's status, and the physician's perceptions of the patient's preferences about the use of life support. We examined the relation between these factors and withdrawal of mechanical ventilation, using Cox proportional-hazards regression analysis. RESULTS: Of 851 patients who were receiving mechanical ventilation, 539 (63.3 percent) were successfully weaned, 146 (17.2 percent) died while receiving mechanical ventilation, and 166 (19.5 percent) had mechanical ventilation withdrawn. The need for inotropes or vasopressors was associated with withdrawal of the ventilator (hazard ratio, 1.78; 95 percent confidence interval, 1.20 to 2.66; P=0.004), as were the physician's prediction that the patient's likelihood of survival in the intensive care unit was less than 10 percent (hazard ratio, 3.49; 95 percent confidence interval, 1.39 to 8.79; P=0.002), the physician's prediction that future cognitive function would be severely impaired (hazard ratio, 2.51; 95 percent confidence interval, 1.28 to 4.94; P=0.04), and the physician's perception that the patient did not want life support used (hazard ratio, 4.19; 95 percent confidence interval, 2.57 to 6.81; P<0.001). CONCLUSIONS: Rather than age or the severity of the illness and organ dysfunction, the strongest determinants of the withdrawal of ventilation in critically ill patients were the physician's perception that the patient preferred not to use life support, the physician's predictions of a low likelihood of survival in the intensive care unit and a high likelihood of poor cognitive function, and the use of inotropes or vasopressors.

Adult↗

Intratracheal pulmonary ventilation keeps tracheal tubes clean without impairing mucociliary transport.

BACKGROUND: Intratracheal pulmonary ventilation (ITPV) is a form of tracheal gas insufflation through a reverse thrust catheter that facilitates expiration and enhances CO2 removal. Tracheas of sheep mechanically ventilated for 3 days with gas delivered through the reverse-thrust catheter remained free of secretions, without suctioning. It was hypothesized that: 1) The expiratory flow from the lungs, combined with continuous cephalad flow from the reverse-thrust catheter keeps endotracheal tubes clean; and 2) tracheal mucus velocity is not impaired by ITPV. METHODS: A model trachea connected to a test lung and to a ventilator, via an 8-mm endotracheal tube, was used. Inspiratory and expiratory peak flow velocities and the movement of mucus in the model trachea and in the endotracheal tube were measured during conventional mechanical ventilation and ITPV. Tracheal mucus velocity was measured radiographically, using tantalum discs as markers, in seven intubated sheep ventilated for one hour with volume-controlled ventilation, and with ITPV. One millilitre Evans Blue dye was introduced into the trachea, to visualize mucus transport into the endotracheal tube. RESULTS: Peak expiratory flow velocity exceeded peak inspiratory flow velocity by 100% during ITPV. During volume-controlled ventilation, flow velocities were equal. During ITPV, there was slow, then rapid cephalad movement of mucus in the model trachea, 0.5 cm distal to the tip of the endotracheal tube, the velocity increasing once mucus entered the endotracheal tube. During volume-controlled ventilation, no movement of mucus was found. Baseline tracheal mucus velocity was equal during volume-controlled ventilation and ITPV. Secretions stained with Evans Blue dye entered the endotracheal tube and were rapidly expelled from within the endotracheal tubes during ITPV; only traces of mucus were found in two sheep during volume-controlled ventilation. CONCLUSION: The enhanced expiratory flow during ITPV expels secretions from the endotracheal tube through entraining of mucus at the tip of the endotracheal tube. Tracheal mucus velocity is not influenced by ITPV.

Animals↗

Haemodynamic features during high-frequency oscillatory ventilation in preterms.

AIM: To compare the haemodynamic status during high-frequency oscillatory ventilation and conventional mechanical ventilation in very preterm infants with respiratory distress syndrome. METHODS: Thirty-two neonates of less than 30 wk gestation randomly assigned to high-frequency oscillatory ventilation (n = 15) or conventional mechanical ventilation (n = 17) had three echocardiographies and one cerebral Doppler-echography under the same ventilation during the first 48 h of life. RESULTS: Mean airway pressure was 2 cm H2O higher in infants ventilated with high-frequency oscillatory ventilation at the different echocardiographies. Comparable right ventricular indexes were observed in the two groups. Reduction of the ductus arteriosus diameter and ductal closure were significant only in neonates ventilated conventionally. Left ventricular performance and left ventricular contractility did not differ between the groups. The high-frequency group had lower end diastolic velocity and a higher resistance index in the anterior cerebral artery. CONCLUSION: Compared with conventional mechanical ventilation, high-frequency oscillatory ventilation was achieved without altering cardiac function. However, the inability of the left ventricle to improve its performance in the presence of a significant ductal shunt suggests a narrow range of optimal pressures under this ventilatory mode.

Blood Flow Velocity↗

Spontaneous minute ventilation is a predictor of extubation failure in extremely-low-birth-weight infants.

OBJECTIVE: To validate the percentage of time spent below a target value of spontaneous expiratory minute ventilation (< 125 ml/min per kg) during a 2-h period of continuous positive airway pressure (CPAP) via an endotracheal tube (ETT) as a predictor of failed extubation in preterm infants. METHODS: Forty-one infants intubated for at least 24 h, with birth weight between 500 and 1000 g, who were clinically stable and at ventilator setting compatible with an extubation attempt, were studied during a 2-h period of ETT CPAP. Dynamic lung compliance and total lung resistance were measured during a period of quiet breathing, while tidal volume (Vt), respiratory rate and the corresponding spontaneous expiratory minute ventilation values were calculated for the complete recording period of 2 h using a customized computer program. The time each patient spent below the target spontaneous expiratory minute ventilation value was reported as a percentage of the total recorded time (% spontaneous expiratory minute ventilation < 125 ml/min per kg). Extubation failure was defined as the need for reintubation within 72 h. RESULTS: Eleven out of 41 babies (26.8%) experienced failure of extubation (failure group) while 30 infants (73.2%) were successfully extubated (success group). There were no significant differences in dynamic lung compliance and lung resistance between the two groups, but the mean values of respiratory rate and spontaneous expiratory minute ventilation were significantly lower in the failure group than in the success group: 43 (37-56) breaths/min and 240 (160-353) ml/min per kg vs. 53 (28-67) breaths/min and 309 (223-434) ml/min per kg, respectively (p = 0.0129 and p = 0.0039). Moreover, the babies in whom extubation failed spent a longer time below the target value of spontaneous expiratory minute ventilation when compared with successfully extubated babies (p < 0.0001). Percentage of time spent with spontaneous expiratory minute ventilation < 125 ml/min per kg had a larger area than transcutaneous (Tc)PCO2, TcPO2 and pulse oxymetry saturation (SpO2) under the receiver operator characteristic curves. CONCLUSION: The measurement of spontaneous expiratory minute ventilation prior to extubation could be useful in identifying those babies who are not ready for spontaneous ventilation.

Biomarkers↗

Studies of ventilation efficiency in a protective isolation room by the use of a scale model.

OBJECTIVE: To assess the ability of a protective isolation room ventilation system to reduce patient exposure to airborne infectious agents, using a small-scale model that permits cost-effective and unobtrusive study of relevant indices of performance. DESIGN: A one-half scale model of a protective isolation room at the University of Minnesota Hospital was constructed and equipped for tracer gas experiments to assess ventilation efficiency. MEASUREMENTS: Tracer gas (SF6) was injected into the model supply air. Tracer gas concentration was recorded over time and analyzed to determine local and room mean age of air. Age of air is a direct measurement of ventilation efficiency and can be used to predict patient exposure to contamination. RESULTS: Although for the room taken as a whole, ventilation efficiency was close to 50% (a value corresponding to perfect mixing), the experimental results for the local mean age of air indicate that some parts of the model were ventilated much better than others. CONCLUSION: Room air exchange rate is only one parameter useful in assessing ventilation in patient areas. Effective distribution of ventilation air also is critical to the control of airborne contamination. Areas of the room with poor ventilation would be expected to have higher concentrations of airborne infectious agents and other contaminants. Patient exposure can be minimized by placing the patient in well-ventilated areas of the room. Improved ventilation designs may reduce patient exposure further without increasing actual airflow rate.

Air Microbiology↗

Evaluation of the Pneupac Ventipac portable ventilator: comparison of performance in a mechanical lung and anaesthetized patients.

The performance of the Pneupac Ventipac portable gas-powered ventilator was evaluated in two stages. The accuracy of delivery of the ventilator was assessed using a mechanical lung model at different combinations of compliance and airway resistance to simulate normal and diseased lungs. The performance of the ventilator was then assessed in 20 anaesthetized patients. The tidal volume delivered by the ventilator in airmix mode (nominal inspiratory oxygen fraction (FIO2) 0.45) was between -20 and +30% of the preset tidal volume with the mechanical lung model adjusted to normal adult values of compliance and airway resistance. The corresponding value with the ventilator set to deliver 100% oxygen was between -22 and -7% of the preset tidal volume. The performance of the ventilator decreased when either compliance was reduced or airway resistance was increased in the mechanical lung model; this effect was greater in airmix mode. Delivered tidal volume was between -19 and +12% of the present tidal volume in the group of anaesthetized patients using the ventilator in airmix mode. The ventilator was reliable and simple to use, and performance was within acceptable limits in the anaesthetized patients. However, we recommend that a means of verifying the adequacy of ventilation should always be used when transporting critically ill or anaesthetized patients with any portable ventilator, particularly when lung compliance or airway resistance may be abnormal.

Adolescent↗

Comparison of NAD 6000 and servo 900C ventilators in an infant lung model.

UNLABELLED: We compared the ability of the NAD 6000 (North American Dräger, Telford, PA) and the Servo 900C (Siemens-Elema AB, Solna, Sweden) anesthesia ventilators to maintain precise delivery of small tidal volumes (V(t)) and positive end-expiratory pressure using an infant test lung model. A variety of ventilator and lung model settings were selected to test clinical conditions simulating normal and extremely compromised lung function. Differences in ventilator output were analyzed by using an independent t-test with P <0.05 considered significant. With the ventilators set to deliver a V(t) of 30 mL, the actual delivered V(t) was significantly better for the NAD 6000 (25 +/- 2 mL) compared with the Servo 900C (18 +/- 3 mL), P <0.001. When the ventilators were set to deliver 100 mL V(t), their delivered V(t) were not significantly different, NAD 6000 (66 +/- 19 mL) and Servo 900C (60 +/- 12 mL), P = 0.09. The exhaled V(t) read by the anesthesia machines was significantly closer to the delivered V(t) for the NAD 6000 (11 +/- 9 mL) compared with the Servo 900C (37 +/- 11 mL), P < 0.001. Both ventilators maintained the end expiratory pressure delivered to the test lung within 2 cm H(2)O of the set positive end-expiratory pressure on average. As the conditions changed requiring the ventilator to develop a higher peak inflating pressure, both ventilators showed a decrease in V(t) delivered, which was proportionate to the tubing compression volume loss. IMPLICATIONS: The NAD 6000 (North American Dräger, Telford, PA) and Servo 900C (Siemens-Elema AB, Solna, Sweden) are able to precisely deliver small Tidal Volumes. They both decreased in performance when tested under extreme conditions. Earlier studies of traditional anesthesia ventilators suggest that the NAD 6000 and Servo 900C are superior pediatric ventilators.

Air Pressure↗

Effects of proportional assist ventilation on inspiratory muscle effort in patients with chronic obstructive pulmonary disease and acute respiratory failure.

BACKGROUND: Acute respiratory failure may develop in patients with chronic obstructive pulmonary disease because of intrinsic positive end-expiratory pressure (PEEPi) and increased resistive and elastic loads. Proportional assist ventilation is an experimental mode of partial ventilatory support in which the ventilator generates flow to unload the resistive burden (flow assistance: FA) and volume to unload the elastic burden (volume assistance: VA) proportionally to inspiratory muscle effort, and PEEPi can be counterbalanced by application of external PEEP. The authors assessed effects of proportional assist ventilation and optimal ventilatory settings in patients with chronic obstructive pulmonary disease and acute respiratory failure. METHODS: Inspiratory muscles and diaphragmatic efforts were evaluated by measurements of esophageal, gastric, and transdiaphragmatic pressures. Minute ventilation and breathing patterns were evaluated by measuring airway pressure and flow. Measurements were performed during spontaneous breathing, continuous positive airway pressure, FA, FA+PEEP, VA, VA+PEEP, FA+VA, and FA+VA+PEEP. RESULTS: FA+PEEP provided the greatest improvement in minute ventilation (89 +/- 3%) and dyspnea (62 +/- 2%). The largest reduction in pressure time product per breath of the respiratory muscles and diaphragm (44 +/- 3% and 33 +/- 2%, respectively) also was observed during FA+PEEP condition. When VA was added to this setting, a reduction in respiratory rate (50 +/- 3%), an increase in inspiratory time (102 +/- 6%), and a further reduction in pressure time product per minute (65 +/- 2% and 64% for the respiratory muscles and diaphragm, respectively) was observed. However, values of pressure time product per liter of minute ventilation during FA+VA+PEEP did not differ with those observed during FA+PEEP condition. Worsening of patient-ventilator interaction and breathing asynchrony occurred when VA was implemented. CONCLUSIONS: Application of PEEP to counterbalance PEEPi and FA to unload the resistive burden provided the optimal conditions in such patients. Ventilator over-assistance and patient-ventilator asynchrony was observed when VA was added to this setting. The clinical use of proportional assist ventilation should be based on continuous measurements of respiratory mechanics.

Acute Disease↗

Air cysts and bronchiectasis prevail in nondependent areas in severe acute respiratory distress syndrome: a computed tomographic study of ventilator-associated changes.

OBJECTIVE: To investigate prevalence and spatial distribution of air cysts and bronchiectasis associated with mechanical ventilation in patients with severe acute respiratory distress syndrome. DESIGN: Retrospective observational study. SETTING: University hospital intensive care division. SUBJECTS: A total of 21 patients with severe acute respiratory distress syndrome requiring prolonged mechanical ventilation and undergoing thoracic computed tomographic scanning. MEASUREMENTS AND MAIN RESULTS: Lung fields were anatomically divided according to functional bronchial divisions in ten segments on each side. Air cysts, bronchiectasis, and the percentage of normal and abnormal tissue were quantified for each segment and correlated to the duration and variables of mechanical ventilation. Air cysts prevailed in nondependent compared with dependent areas (38% +/- 5% vs. 9% +/- 3%, respectively; p <.01). With mechanical ventilation longer than 10 days, the odds ratio was 13.1 (95% confidence interval, 1.4-118.7) for air cysts and for bronchiectasis 17.6 (95% confidence interval, 2.8-109.6). The amount of abnormal parenchyma correlated with duration of mechanical ventilation on high end-inspiratory pressure but not with tidal volume or minute ventilation. The presence of pneumothorax was not correlated with ventilation settings but with the amount of consolidated tissue revealed by the computed tomographic scan. CONCLUSIONS: These findings suggest predominant ventilator-induced lung damage in better ventilated areas (i.e., nondependent regions). Severity of changes revealed by computed tomographic imaging seems to be associated mainly with the high inspiratory pressures required and the length of mechanical ventilation.

APACHE↗

Statistical evaluation of ventilator-free days as an efficacy measure in clinical trials of treatments for acute respiratory distress syndrome.

OBJECTIVE: Trials of potential new therapies in acute lung injury are difficult and expensive to conduct. This article is designed to determine the utility, behavior, and statistical properties of a new primary end point for such trials, ventilator-free days, defined as days alive and free from mechanical ventilation. Describing the nuances of this outcome measure is particularly important because using it, while ignoring mortality, could result in misleading conclusions. DESIGN: To develop a model for the duration of ventilation and mortality and fit the model by using data from a recently completed clinical trial. To determine the appropriate test statistic for the new measure and derive a formula for power. To determine a formula for the probability that the test statistic will reject the null hypothesis and mortality will simultaneously show improvement. To plot power curves for the test statistic and determine sample sizes for reasonable alternative hypotheses. SETTING: Intensive care units. PATIENTS: Patients with acute respiratory distress syndrome or acute lung injury as defined by the American-European Consensus Conference. MAIN RESULTS: The proposed model fit the clinical data. Ventilator-free days were improved by lower tidal volume ventilation, but the improvement was mostly caused by the improved mortality rate, so trials that expected similar effects would only have modest increase in power if they used ventilator-free days as their primary end point rather than 28-day mortality. Similar results were obtained using the model in two groups segregated by low or high Acute Physiology and Chronic Health Evaluation score. On the other hand, if patients are divided into two groups on the basis of the lung injury score, both the duration of ventilation and mortality are lower in the low lung injury score group. A trial of a treatment that had a similar clinical effect would have a large increase in power, allowing for a reduction in the required sample size. CONCLUSIONS: Use of ventilator-free days as a trial end point allows smaller sample sizes if it is assumed that the treatment being tested simultaneously reduces the duration of ventilation and improves mortality. It is unlikely that a treatment that led to higher mortality could lead to a statistically significant improvement in ventilator-free days. This would be especially true if the treatment were also required to produce a nominal improvement in mortality.

APACHE↗

Effects of cyclic opening and closing at low- and high-volume ventilation on bronchoalveolar lavage cytokines.

OBJECTIVE: To examine the mechanisms of ventilator-induced lung injury at low and high lung volumes. DESIGN: Prospective, randomized, laboratory study. SETTING: University research laboratory. SUBJECTS: Eighty-eight adult male Sprague-Dawley rats. INTERVENTIONS: Mechanical ventilation using low and high lung volumes. MEASUREMENTS AND MAIN RESULTS: An ex vivo rat lung model was used. In study I (ventilation at low lung volumes), rat lungs (n = 40) were randomly assigned to various modes of ventilation: a) opening and closing with positive end-expiratory pressure (PEEP; control): tidal volume 7 mL/kg and PEEP 5 cm H2O; b) opening and closing from zero end-expiratory pressure (ZEEP): tidal volume 7 mL/kg and PEEP 0; or c) atelectasis. Peak inspiratory pressure was monitored at the beginning and end of 3 hrs of ventilation. At the end of 3 hrs of ventilation, the lungs were lavaged, and the concentrations of tumor necrosis factor-alpha, macrophage inflammatory protein-2, and interleukin-6 cytokines were measured in the lavage. In study II (ventilation at high volumes), rat lungs (n = 45) were randomly assigned to a) cyclic lung stretch: pressure-controlled ventilation, peak inspiratory pressure 50 cm H2O, and PEEP 8 cm H2O; b) continuous positive airway pressure at 50 cm H2O (CPAP50); or c) CPAP at the mean airway pressure of the cyclic stretch group (CPAP 31 cm H2O). Bronchoalveolar lavage cytokine concentrations (tumor necrosis factor-alpha, macrophage inflammatory protein-2, and interleukin-6) were measured at the end of 3 hrs of ventilation. In the low volume study, there was no difference in bronchoalveolar lavage cytokine concentrations between the PEEP group and the atelectatic group. All cytokines were significantly higher in the ZEEP group compared with the atelectasis group. Macrophage inflammatory protein-2 was significantly higher in the ZEEP group compared with the PEEP group. Lung compliance, as reflected by change in peak inspiratory pressure, was also significantly worse in the ZEEP compared with the PEEP group. In the high-volume study, tumor necrosis factor-alpha and interleukin-6 were significantly higher in the cyclic stretch group compared with the CPAP 31 group. There was no significant difference between the cytokine concentrations in the cyclic stretch group compared with the CPAP 50 group. CONCLUSION: We conclude that at low lung volumes, cyclic opening and closing from ZEEP leads to greater increases in bronchoalveolar lavage cytokines than atelectasis. With high-volume ventilation, over time, the degree of overdistension is more associated with increases in bronchoalveolar lavage cytokines than cyclic opening and closing alone.

Animals↗

Modulation and treatment of patient-ventilator dyssynchrony.

PURPOSE OF REVIEW: The coupling between ventilator delivered inspiratory flow and patient's demands both in terms of timing and drive is a challenging task that has become largely feasible in recent years. This review addresses the new advances to modulate and treat patient-ventilator dyssynchrony. RECENT FINDINGS: Patient-ventilator dyssynchrony is a common phenomenon with conventional modes of mechanical ventilation which influence the duration of mechanical ventilation. Inspection of pressure, volume and flow waveforms represents a valuable tool for the physician to recognize and take the appropriate action to improve patient-ventilator synchrony. New developments have been introduced aiming to improve patient ventilator synchrony by modulating the triggering function and the variables that control the flow delivery and the cycling off. SUMMARY: Patient-ventilator dyssynchrony may affect patients' outcome. New modes of assisted mechanical ventilation have been introduced and represent a major step forward in modulating patient-ventilator dyssynchrony.

Critical Care↗